TABLE 1.
Significantly Enriched (P < 0.01) Biologic Processes and Signal Transduction Pathways in Response to 225Ac-PP-F11N Treatment
| 225Ac-PP-F11N | Fold enrichment | P |
|---|---|---|
| DDR, repair and nucleus structure | ||
| DNA replication (BRCA1, POLA2, RAD50, RAD9A, RBBP8, SET, TICRR, WRN, CDT1, CHTF18, CLSPN, MCM2, MCM3AP, MCM3, MCM6, NBN, RFC1, SSRP1, TOPBP1) GOTERM_BP | 9.1 | 3.1E−12 |
| DNA repair (BRCA1, RAD50, RAD51AP1, RAD9A, RBBP8, TICRR, WRN, BOD1L1, CLSPN, NBN, NPM1, SMC1A, SSRP1, TOPBP1, TRIM28) GOTERM_BP | 4.7 | 3.8E−6 |
| Double-strand break repair via nonhomologous end joining (BRCA1, H2AFX, RAD50, WHSC1, MDC1, NBN, TP53BP1, UIMC1) GOTERM_BP | 9.4 | 2.1E−5 |
| Double-strand break repair via homologous recombination (BRCA1, H2AFX, RAD50, RAD51AP1, RBBP8, XRCC1, NBN, NUCKS1) GOTERM_BP | 8.0 | 6.1E−5 |
| Strand displacement (BRCA1, RAD50, RAD51AP1, RBBP8, WRN, NBN) GOTERM_BP | 17.1 | 2.2E−5 |
| DNA damage checkpoint (H2AFX, RAD9A, CLSPN, MAPK14, NBN, TP53BP1) GOTERM_BP | 14.8 | 4.6E−5 |
| DNA synthesis involved in DNA repair (BRCA1, RAD50, RAD51AP1, RBBP8, WRN, NBN) GOTERM_BP | 12.7 | 9.9E−5 |
| DNA unwinding involved in DNA replication (HMGA1, MCM2, MCM6, TOP2A) GOTERM_BP | 29.6 | 2.7E−4 |
| DNA double-strand break processing (BRCA1, RAD50, RBBP8, NBN) GOTERM_BP | 19.7 | 9.7E−4 |
| DNA duplex unwinding (RAD50, WRN, CHD4, MCM3, NBN) GOTERM_BP | 8.4 | 2.8E−3 |
| Nucleosome assembly (H2AFX, SET, ASF1B, HIST1H1D, HIST1H1E, MCM2, NPM1, NAP1L4) GOTERM_BP | 5.0 | 1.1E−3 |
| Telomere maintenance via telomerase (RAD50, RFC1, TNKS1BP1, TERF2) GOTERM_BP | 16.4 | 1.7E−3 |
| Covalent chromatin modification (RB1, RBL1, ASF1B, CBX3, C17orf49, TRIM28, ZMYND11) GOTERM_BP | 4.6 | 4.3E−3 |
| Telomere maintenance via recombination (POLA2, RAD50, WRN, RFC1) GOTERM_BP | 9.2 | 9.0E−3 |
| Cell cycle regulation | ||
| Cell division (CD2AP, RBBP8, RB1, TPX2, TRIOBP, WAPL, ARPP19, CDC20, CDC23, CDCA2, CCNF, DYNC1LI1, ENSA, HELLS, KIF20B, KIF2A, MAP4, MISP, NUMA1, PSRC1, PKN2, SMC1A, ZC3HC1) GOTERM_BP | 4.9 | 2.2E−9 |
| Mitotic nuclear division (CD2AP, RBBP8, TPX2, TRIOBP, ARPP19, CDC20, CDC23, CDCA2, CCNF, DYNC1LI1, ENSA, HELLS, INCENP, KIF20B) GOTERM_BP | 5.4 | 4.5E−8 |
| Meiotic cell cycle (H2AFX, RBBP8, RBM7, NBN, NUMA1, ZNF318) GOTERM_BP | 13.1 | 8.6E−5 |
| Cell cycle (BRCA1, HJURP, RBL1, CDC20, CHTF18, LIN54, MCM2, NOLC1, PKN2, TERF2, TP53, ZMYND11) GOTERM_BP | 4.1 | 1.8E−4 |
| G1/S transition of mitotic cell cycle (POLA2, RANBP1, RBBPB8, RB1, CDT1, MCM2, MCM3, MCM6) GOTERM_BP | 5.8 | 4.6E−4 |
| Regulation of cell cycle (JUND, MYBL2, RB1, RBL1, CCNF, FIGNL1, LIN54, MED1) GOTERM_BP | 4.8 | 1.4E−3 |
| G2 DNA damage checkpoint (BRCA1, RBBP8, CLSPN, UIMC1) GOTERM_BP | 14.8 | 2.3E−3 |
| Cell cycle checkpoint (RBBP8, RB1, TICRR) GOTERM_BP | 24.7 | 6.1E−3 |
| Mitotic cell cycle checkpoint (RB1, TTK, NBN, SMC1A) GOTERM_BP | 9.2 | 9.0E−3 |
| Mitotic spindle organization (TTK, KIF2A, MAP4, STMN1, SMC1A) GOTERM_BP | 12.3 | 6.7E−4 |
| Chromosome segregation (BRCA1, HJURP, CDCA2, INCENP, PPP1R7, TOP2A) GOTERM_BP | 6.5 | 2.2E−3 |
| Sister chromatid cohesion (AHCTF1, RANBP2, WAPL, CDC20, INCENP, KIF2A, SMC1A) GOTERM_BP | 5.0 | 2.7E−3 |
| Signal transduction and cellular response | ||
| Regulation of signal transduction by p53 class mediator (BRCA1, RAD50, RAD9A, RBBP8, TPX2, WRN, CHD4, MAPK14, NBN, SSRP1, TOPBP1, TP53) GOTERM_BP | 7.2 | 9.2E−7 |
| Cellular response to DNA damage stimulus (BRCA1, H2AFX, LYN, RAD50, RAD9A, TIGAR, WRN, BOD1L1, BAZ1B, TOP2A, TOPBP1, TP53BP1, TP53) GOTERM_BP | 4.6 | 2.6E−5 |
| Response to ionizing radiation (BRCA1, EYA3, H2AFX, TICRR, MTA1, TOPBP1, UIMC1) GOTERM_BP | 10.6 | 4.8E−5 |
| Cellular response to ionizing radiation (RAD51AP1, RAD9A, FIGNL1, MAPK14, TP53) GOTERM_BP | 11.9 | 7.6E−4 |
| Cellular response to epidermal growth factor stimulus (ERRFI1, ZFP36L2, ZFP36, EGFR, MED1) GOTERM_BP | 11.2 | 9.6E−4 |
| Cellular response to dexamethasone stimulus (ERRFI1, CBX3, EGFR, HNRNPU) GOTERM_BP | 10.2 | 6.8E−3 |
| DDR, signal transduction by p53 class mediator resulting in cell cycle arrest (GTSE1, NPM1, TNKS1BP1, TFDP1, TP53) GOTERM_BP | 6.0 | 9.7E−3 |
| ATM signaling pathway (BRCA1, RAD50, RBBP8, NBN, TP53) BIOCARTA | 8.6 | 2.0E−3 |
| Role of BRCA1, BRCA2, and ATM- and Rad3-related in cancer susceptibility (BRCA1, RAD50, RAD9A, NBN, TP53) BIOCARTA | 8.2 | 2.4E−3 |